During that last 4 years we screened 13,876 eligible Tanzanian pregnant women for HIV infection and enrolled and followed up 1085 consenting HIV-positive subjects. Women were randomized in a 2x2 factorial design to vitamin A alone, multivitamins including vitamin A, multivitamins excluding vitamin A, or placebo. Laboratory analyses to determine the effect of the supplements on vertical transmission of HIV are ongoing. We examined the effect of the supplements on secondary endpoints for which data were complete (adverse pregnancy outcomes and T-cell subsets). Women who received multivitamins experienced a significant and sustained increase in CD4 and CD8 cell counts. We propose to continue following up mothers and children beyond the end date of field activities in the current cycle (1/31/1999). Given that CD4 and CD8 counts are far from perfect surrogate markers for disease progression, it is important to ascertain whether the supplements result in improvement in clinical condition or survival of patients. We also propose to follow up the children born to these mothers to prospectively examine the relationships between biochemical and dietary measures of vitamins A, E, B12, and selenium and progression to AIDS among infected children; and between these nutrients and morbidity (diarrheal disease and lower respiratory infections), growth retardation, and mortality among HIV infected and uninfected children. In preliminary analyses of the current study, we also observed substantial prevalence of HIV-1 subtypes, A, C, D, and recombinants. Limited data from other studies suggest that different HIV-1 subtypes may have different pathogenic potentials. We propose to expand the scope of work beyond our original nutritional aims to take advantage of a rare opportunity to examine if HIV-1 subtypes are associated with different rates of vertical transmission or with differential rates of disease progression, findings that are relevant for the design of vaccines. We have demonstrated during the first 4 years that the women in the study are prepared to participate in the proposed activities, that we can adhere to the research schedule, maintain a high rate of follow up (our annual loss to follow up is only 6 percent), and can manage and analyze the data as it becomes available. Given the fast rate of disease progression among HIV- positive children and adults in developing countries, and the limited resources available to address this condition, low cost interventions including micronutrients and effective vaccines are urgently needed for developing countries.